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| Dissertation / PhD Thesis/Book | PreJuSER-28651 |
2003
Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag
Jülich
Please use a persistent id in citations: http://hdl.handle.net/2128/228
Report No.: Juel-4045
Abstract: This dissertation includes two independent studies that investigate two complementary aspects of functional connectivity, i .e. context-invariance and context-specificity, in the Macaque and the human brain. In the first study, a computational meta-analysis of published electrophysiological data an context-independent functional brain connectivity was conducted by means of three independent methods. Almost 4,000 individual experimental findings an interactions between areas of the Macaque cortex (obtained by strychnine neuronography) were analyzed. The independent analyses gave compatible results and showed that (i) the network of functional interactions between cortical areas showed clear small world" characteristics (i.e. a strongly clustered structure with short average path length), and that (ii) this structure contained three main functional clusters, i.e. sensorimotor, visual, and orbito-temporo-insular groups of areas. This study thus provided first evidence for a functional small world" architecture of the primate cortical network. This type of architecture had previously been postulated in the literature, but had not been directly demonstrated. The second study investigated the effects of the atypical antipsychotic substance olanzapine an the functional connectivity of the cerebellum during a simple motor task (self-paced finger tapping). Six schizophrenic patients and six control subjects matched for age and sex were investigated by functional magnetic resonance imaging (fMRI) twice. At the time of the first scan, patents were not medicated; the second scan took place after three weeks of medication by olanzapine. The analyses of the fMRI data showed that, in the context of the investigated motor task, (i) olanzapine led to pronounced changes of cerebellar functional connectivity (CFC) in various brain regions. A major part of three changes were found throughout the prefrontal cortex and the mediodorsal thalamus. These findings are relevant for the concept of "cognitive dysmetria". (ii) significant CFC changes in motor areas were found both within the patient group after medication as well as in the non-medicated control group after repetition of the experiment. Therefore, they may correspond to unspecific repetition effects rather than effects due to olanzapine. In a subsequent analysis that took the repetition into account no significant CFC changes were found in motor regions. (iii) olanzapine normalized the CFC patterns of the patients for the right, but not for the left cerebellum. This study provided the first experimental data an the effects of atypical antipsychotic agents an functional brain connectivity and demonstrated pronounced olanzapine-dependent changes of functional couplings between cerebellum, thalamus, and prefrontal cortex.
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